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Regulated degradation of yeast ornithine decarboxylase

C Toth1, P Coffino

  • 1Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California 94143-0414, USA.

The Journal of Biological Chemistry
|August 28, 1999
PubMed

Insights

Polyamines accelerate the degradation of ornithine decarboxylase (ODC) in yeast, reducing its half-life. This degradation process involves the proteasome, crucial for regulating polyamine levels.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Ornithine decarboxylase (ODC) activity is regulated by polyamines, its downstream products, to prevent excess production.
  • While polyamine-induced ODC degradation is known in animal cells, it remained unconfirmed in yeast (Saccharomyces cerevisiae).

Purpose of the Study:

  • To investigate the mechanism of ornithine decarboxylase (ODC) down-regulation in Saccharomyces cerevisiae.
  • To determine if polyamines induce ODC degradation in yeast and identify the cellular machinery involved.

Main Methods:

  • Pulse-chase analysis was employed to track the degradation rate of newly synthesized ODC.
  • Experiments utilized proteasome mutants to assess the role of the proteasome in ODC regulation.

Main Results:

  • Polyamines significantly decrease the half-life of newly synthesized ODC from 3 hours to approximately 10 minutes.
  • Both newly synthesized and bulk ODC pools exhibit accelerated degradation in the presence of polyamines.
  • Proteasome mutants displayed impaired or absent regulatory responses, indicating the proteasome's essential role.

Conclusions:

  • Induced degradation is the primary mechanism for ODC activity reduction in yeast, mediated by polyamines.
  • The proteasome, including its core and regulatory cap, is critical for polyamine-induced ODC degradation in yeast.
  • A maturation process confers partial resistance to degradation on newly synthesized ODC.

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